Glutathionylation of the L-type Ca2+ Channel in Oxidative Stress-Induced Pathology of the Heart

There is mounting evidence to suggest that protein glutathionylation is a key process contributing to the development of pathology. Glutathionylation occurs as a result of posttranslational modification of a protein and involves the addition of a glutathione moiety at cysteine residues. Such modification can occur on a number of proteins, and exerts a variety of functional consequences. The L-type Ca²⁺ channel has been identified as a glutathionylation target that participates in the development of cardiac pathology. Ca²⁺ influx via the L-type Ca²⁺ channel increases production of mitochondrial reactive oxygen species (ROS) in cardiomyocytes during periods of oxidative stress. This induces a persistent increase in channel open probability, and the resulting constitutive increase in Ca²⁺ influx amplifies the cross-talk between the mitochondria and the channel. Novel strategies utilising targeted peptide delivery to uncouple mitochondrial ROS and Ca²⁺ flux via the L-type Ca²⁺ channel following ischemia-reperfusion have delivered promising results, and have proven capable of restoring appropriate mitochondrial function in myocytes and in vivo.     

Role of microglia in oxidative toxicity associated with encephalomycarditis virus infection in the central nervous system

The single-stranded RNA encephalomyocarditis virus (EMCV) can replicate in the central nervous system (CNS) and lead to prominent brain lesions in the stratum pyramidale hippocampus and the stratum granulosum cerebelli. Activated microglia cells infected by EMCV produce a massive burst of reactive oxygen species (ROS) via NADPH oxidase 2 (NOX2) activation, leading to neuronal death. Balancing this effect is mechanisms by which ROS are eliminated from the CNS. Cellular prion protein (PrP(C)) plays an important antioxidant role and contributes to cellular defense against EMCV infection. This review introduces recent knowledge on brain injury induced by EMCV infection via ROS generation as well as the involvement of various mediators and regulators in the pathogenesis.     

Inflammation, oxidative stress, and obesity

Obesity is a chronic disease of multifactorial origin and can be defined as an increase in the accumulation of body fat. Adipose tissue is not only a triglyceride storage organ, but studies have shown the role of white adipose tissue as a producer of certain bioactive substances called adipokines. Among adipokines, we find some inflammatory functions, such as Interleukin-6 (IL-6); other adipokines entail the functions of regulating food intake, therefore exerting a direct effect on weight control. This is the case of leptin, which acts on the limbic system by stimulating dopamine uptake, creating a feeling of fullness. However, these adipokines induce the production of reactive oxygen species (ROS), generating a process known as oxidative stress (OS). Because adipose tissue is the organ that secretes adipokines and these in turn generate ROS, adipose tissue is considered an independent factor for the generation of systemic OS. There are several mechanisms by which obesity produces OS. The first of these is the mitochondrial and peroxisomal oxidation of fatty acids, which can produce ROS in oxidation reactions, while another mechanism is over-consumption of oxygen, which generates free radicals in the mitochondrial respiratory chain that is found coupled with oxidative phosphorylation in mitochondria. Lipid-rich diets are also capable of generating ROS because they can alter oxygen metabolism. Upon the increase of adipose tissue, the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), was found to be significantly diminished. Finally, high ROS production and the decrease in antioxidant capacity leads to various abnormalities, among which we find endothelial dysfunction, which is characterized by a reduction in the bioavailability of vasodilators, particularly nitric oxide (NO), and an increase in endothelium-derived contractile factors, favoring atherosclerotic disease.     

Oxidative stress: the role of cytochromes P450 in oxygen activation

Oxidative stress is associated with a number of degenerative disease states, such as cancer and AIDS. Fundamental to oxidative stress is the generation of superoxide, peroxide and other reactive oxygen species (ROS). This review focuses on the importance of cytochrome P450 (CYP) enzymes in the activation of oxygen and ROS generation, together with a discussion of defence mechanisms which can offer protection against oxidative stress. © 2002 Society of Chemical Industry.     

Ascorbate–Glutathione Oxidant Scavengers,Metabolome Analysis and Adaptation Mechanisms of Ion Exclusion in Sorghum under Salt Stress

Salt stress is one of the major significant restrictions that hamper plant development and agriculture ecosystems worldwide. Novel climate-adapted cultivars and stress tolerance-enhancing molecules are increasingly appreciated to mitigate the detrimental impacts of adverse stressful conditions. Sorghum is a valuable source of food and a potential model for exploring and understanding salt stress dynamics in cereals and for gaining a better understanding of their physiological pathways. Herein, we evaluate the antioxidant scavengers, photosynthetic regulation, and molecular mechanism of ion exclusion transporters in sorghum genotypes under saline conditions. A pot experiment was conducted in two sorghum genotypes viz. SSG 59-3 and PC-5 in a climate-controlled greenhouse under different salt concentrations (60, 80, 100, and 120 mM NaCl). Salinity drastically affected the photosynthetic machinery by reducing the accumulation of chlorophyll pigments and carotenoids. SSG 59-3 alleviated the adverse effects of salinity by suppressing oxidative stress (H₂O₂) and stimulating enzymatic and non-enzymatic antioxidant activities (SOD, APX, CAT, POD, GR, GST, DHAR, MDHAR, GSH, ASC, proline, GB), as well as protecting cell membrane integrity (MDA, electrolyte leakage). Salinity also influenced Na⁺ ion efflux and maintained a lower cytosolic Na⁺/K⁺ ratio via the concomitant upregulation of SbSOS1, SbSOS2, and SbNHX-2 and SbV-Ppase-II ion transporter genes in sorghum genotypes. Overall, these results suggest that Na⁺ ions were retained and detoxified, and less stress impact was observed in mature and younger leaves. Based on the above, we deciphered that SSG 59-3 performed better by retaining higher plant water status, photosynthetic assimilates and antioxidant potential, and the upregulation of ion transporter genes and may be utilized in the development of resistant sorghum lines in saline regions.     

Triphenylphosphonium (TPP)-Based Antioxidants: A New Perspective on Antioxidant Design

Mitochondrial oxidative damage and dysfunction contribute to a wide range of human diseases. Considering the limitation of conventional antioxidants and that mitochondria are the main source of reactive oxygen species (ROS) which induce oxidative damage, mitochondria-targeted antioxidants which can selectively block mitochondrial oxidative damage and prevent various types of cell death have been widely developed. As a lipophilic cation, triphenylphosphonium (TPP) has been commonly used in designing mitochondria-targeted antioxidants. Conjugated with the TPP moiety, antioxidants can achieve more than 1000-fold higher mitochondrial concentration depending on cell membrane potentials and mitochondrial membrane potentials. Herein we discuss the deficiencies of conventional antioxidants and the advantages of mitochondrial targeting, and review various types of TPP-based mitochondria-targeted antioxidants. These provide theoretical and background support for the design of new anti-oxidant.     

Molecular Mechanisms of Nitric Oxide (NO) Signaling and Reactive Oxygen Species (ROS) Homeostasis during Abiotic Stresses in Plants

Abiotic stressors, such as drought, heavy metals, and high salinity, are causing huge crop losses worldwide. These abiotic stressors are expected to become more extreme, less predictable, and more widespread in the near future. With the rapidly growing human population and changing global climate conditions, it is critical to prevent global crop losses to meet the increasing demand for food and other crop products. The reactive gaseous signaling molecule nitric oxide (NO) is involved in numerous plant developmental processes as well as plant responses to various abiotic stresses through its interactions with various molecules. Together, these interactions lead to the homeostasis of reactive oxygen species (ROS), proline and glutathione biosynthesis, post-translational modifications such as S-nitrosylation, and modulation of gene and protein expression. Exogenous application of various NO donors positively mitigates the negative effects of various abiotic stressors. In view of the multidimensional role of this signaling molecule, research over the past decade has investigated its potential in alleviating the deleterious effects of various abiotic stressors, particularly in ROS homeostasis. In this review, we highlight the recent molecular and physiological advances that provide insights into the functional role of NO in mediating various abiotic stress responses in plants.     

Mitogen-Activated Protein (MAP) Kinases in Plant Metal Stress: Regulation and Responses in Comparison to Other Biotic and Abiotic Stresses

Exposure of plants to toxic concentrations of metals leads to disruption of the cellular redox status followed by an accumulation of reactive oxygen species (ROS). ROS, like hydrogen peroxide, can act as signaling molecules in the cell and induce signaling via mitogen-activated protein kinase (MAPK) cascades. MAPK cascades are evolutionary conserved signal transduction modules, able to convert extracellular signals to appropriate cellular responses. In this review, our current understanding about MAPK signaling in plant metal stress is discussed. However, this knowledge is scarce compared to research into the role of MAPK signaling in the case of other abiotic and biotic stresses. ROS production is a common response induced by different stresses and undiscovered analogies may exist with metal stress. Therefore, further attention is given to MAPK signaling in other biotic and abiotic stresses and its interplay with other signaling pathways to create a framework in which the involvement of MAPK signaling in metal stress may be studied.     

Friend or Foe: The Relativity of (Anti)oxidative Agents and Pathways

An element, iron, a process, the generation of reactive oxygen species (ROS), and a molecule, ascorbate, were chosen in our study to show their dual functions and their role in cell fate decision. Iron is a critical component of numerous proteins involved in metabolism and detoxification. On the other hand, excessive amounts of free iron in the presence of oxygen can promote the production of potentially toxic ROS. They can result in persistent oxidative stress, which in turn can lead to damage and cell death. At the same time, ROS—at strictly regulated levels—are essential to maintaining the redox homeostasis, and they are engaged in many cellular signaling pathways, so their total elimination is not expedient. Ascorbate establishes a special link between ROS generation/elimination and cell death. At low concentrations, it behaves as an excellent antioxidant and has an important role in ROS elimination. However, at high concentrations, in the presence of transition metals such as iron, it drives the generation of ROS. In the term of the dual function of these molecules and oxidative stress, ascorbate/ROS-driven cell deaths are not necessarily harmful processes—they can be live-savers too.     

UV-Induced Cell Death in Plants

Plants are photosynthetic organisms that depend on sunlight for energy. Plants respond to light through different photoreceptors and show photomorphogenic development. Apart from Photosynthetically Active Radiation (PAR; 400–700 nm), plants are exposed to UV light, which is comprised of UV-C (below 280 nm), UV-B (280–320 nm) and UV-A (320–390 nm). The atmospheric ozone layer protects UV-C radiation from reaching earth while the UVR8 protein acts as a receptor for UV-B radiation. Low levels of UV-B exposure initiate signaling through UVR8 and induce secondary metabolite genes involved in protection against UV while higher dosages are very detrimental to plants. It has also been reported that genes involved in MAPK cascade help the plant in providing tolerance against UV radiation. The important targets of UV radiation in plant cells are DNA, lipids and proteins and also vital processes such as photosynthesis. Recent studies showed that, in response to UV radiation, mitochondria and chloroplasts produce a reactive oxygen species (ROS). Arabidopsis metacaspase-8 (AtMC8) is induced in response to oxidative stress caused by ROS, which acts downstream of the radical induced cell death (AtRCD1) gene making plants vulnerable to cell death. The studies on salicylic and jasmonic acid signaling mutants revealed that SA and JA regulate the ROS level and antagonize ROS mediated cell death. Recently, molecular studies have revealed genes involved in response to UV exposure, with respect to programmed cell death (PCD).     

Impaired mitochondrial respiratory functions and oxidative stress in streptozotocin-induced diabetic rats

We have previously shown a tissue-specific increase in oxidative stress in the early stages of streptozotocin (STZ)-induced diabetic rats. In this study, we investigated oxidative stress-related long-term complications and mitochondrial dysfunctions in the different tissues of STZ-induced diabetic rats (>15 mM blood glucose for 8 weeks). These animals showed a persistent increase in reactive oxygen and nitrogen species (ROS and RNS, respectively) production. Oxidative protein carbonylation was also increased with the maximum effect observed in the pancreas of diabetic rats. The activities of mitochondrial respiratory enzymes ubiquinol: cytochrome c oxidoreductase (Complex III) and cytochrome c oxidase (Complex IV) were significantly decreased while that of NADH:ubiquinone oxidoreductase (Complex I) and succinate:ubiquinone oxidoreductase (Complex II) were moderately increased in diabetic rats, which was confirmed by the increased expression of the 70 kDa Complex II sub-unit. Mitochondrial matrix aconitase, a ROS sensitive enzyme, was markedly inhibited in the diabetic rat tissues. Increased expression of oxidative stress marker proteins Hsp-70 and HO-1 was also observed along with increased expression of nitric oxide synthase. These results suggest that mitochondrial respiratory complexes may play a critical role in ROS/RNS homeostasis and oxidative stress related changes in type 1 diabetes and may have implications in the etiology of diabetes and its complications.     

Epigallocatechin Gallate for Management of Heavy Metal-Induced Oxidative Stress: Mechanisms of Action,Efficacy, and Concerns

In this review, we highlight the effects of epigallocatechin gallate (EGCG) against toxicities induced by heavy metals (HMs). This most active green tea polyphenol was demonstrated to reduce HM toxicity in such cells and tissues as testis, liver, kidney, and neural cells. Several protective mechanisms that seem to play a pivotal role in EGCG-induced effects, including reactive oxygen species scavenging, HM chelation, activation of nuclear factor erythroid 2-related factor 2 (Nrf2), anti-inflammatory effects, and protection of mitochondria, are described. However, some studies, especially in vitro experiments, reported potentiation of harmful HM actions in the presence of EGCG. The adverse impact of EGCG on HM toxicity may be explained by such events as autooxidation of EGCG, EGCG-mediated iron (Fe³⁺) reduction, depletion of intracellular glutathione (GSH) levels, and disruption of mitochondrial functions. Furthermore, challenges hampering the potential EGCG application related to its low bioavailability and proper dosing are also discussed. Overall, in this review, we point out insights into mechanisms that might account for both the beneficial and adverse effects of EGCG in HM poisoning, which may have a bearing on the design of new therapeutics for HM intoxication therapy.     

Looking into a Conceptual Framework of ROS–miRNA–Atrial Fibrillation

Atrial fibrillation (AF) has been recognized as a major cause of cardiovascular-related morbidity and mortality. MicroRNAs (miRNAs) represent recent additions to the collection of biomolecules involved in arrhythmogenesis. Reactive oxygen species (ROS) have been independently linked to both AF and miRNA regulation. However, no attempts have been made to investigate the possibility of a framework composed of ROS–miRNA–AF that is related to arrhythmia development. Therefore, this review was designed as an attempt to offer a new approach to understanding AF pathogenesis. The aim of this review was to find and to summarize possible connections that exist among AF, miRNAs and ROS to understand the interactions among the molecular entities underlying arrhythmia development in the hopes of finding unappreciated mechanisms of AF. These findings may lead us to innovative therapies for AF, which can be a life-threatening heart condition. A systemic literature review indicated that miRNAs associated with AF might be regulated by ROS, suggesting the possibility that miRNAs translate cellular stressors, such as ROS, into AF pathogenesis. Further studies with a more appropriate experimental design to either prove or disprove the existence of an ROS–miRNA–AF framework are strongly encouraged.     

羟丙基甲基纤维素的体外自由基降解研究

通过Fenton-AH-H2O2体系模拟体内的活性氧簇自由基(ROS)条件对美容填充辅料羟丙基甲基纤维素(HPMC)进行降解,研究了降解过程中HPMC分子量与动力粘度的变化。结果发现,在降解过程中,E3-HPMC与E50-HPMC的分子量均下降了90%,E4M-HPMC的动力粘度下降了75%,E10M-HPMC的动力粘度下降了40%。表明ROS对HPMC具有显著的降解作用。     

Oxidative Stress in Cardiovascular Disease

In the special issue “Oxidative Stress in Cardiovascular Disease” authors were invited to submit papers that investigate key questions in the field of cardiovascular free radical biology. The original research articles included in this issue provide important information regarding novel aspects of reactive oxygen species (ROS)-mediated signaling, which have important implications in physiological and pathophysiological cardiovascular processes. The issue also included a number of review articles that highlight areas of intense research in the fields of free radical biology and cardiovascular medicine.     

Mitochondrial adaptations to oxidative stress confer resistance to apoptosis in lymphoma cells

Acquired resistance to drugs commonly used for lymphoma treatment poses a significant barrier to improving lymphoma patient survival. Previous work with a lymphoma tissue culture model indicates that selection for resistance to oxidative stress confers resistance to chemotherapy-induced apoptosis. This suggests that adaptation to chronic oxidative stress can contribute to chemoresistance seen in lymphoma patients. Oxidative stress-resistant WEHI7.2 cell variants in a lymphoma tissue culture model exhibit a range of apoptosis sensitivities. We exploited this phenotype to test for mitochondrial changes affecting sensitivity to apoptosis in cells made resistant to oxidative stress. We identified impaired release of cytochrome c, and the intermembrane proteins adenylate kinase 2 and Smac/DIABLO, indicating inhibition of the pathway leading to permeabilization of the outer mitochondrial membrane. Blunting of a glucocorticoid-induced signal and intrinsic mitochondrial resistance to cytochrome c release contributed to both points of resistance. The level of Bcl-2 family members or a difference in Bim induction were not contributing factors. The extent of cardiolipin oxidation following dexamethasone treatment, however, did correlate with apoptosis resistance. The differences found in the variants were all proportionate to the degree of resistance to glucocorticoid treatment. We conclude that tolerance to oxidative stress leads to mitochondrial changes that confer resistance to apoptosis.